Melphalan and Busulfan Followed By Donor Peripheral Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Multiple Myeloma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00313625
First received: April 11, 2006
Last updated: September 20, 2010
Last verified: September 2010
  Purpose

RATIONALE: Giving chemotherapy, such as melphalan and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus and methotrexate before or after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving melphalan together with busulfan followed by donor peripheral stem cell transplant, tacrolimus, and methotrexate works in treating patients with multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: busulfan
Drug: melphalan
Drug: methotrexate
Drug: tacrolimus
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Intravenous Melphalan and Busulfan Followed by HLA-Matched, Allogeneic Peripheral Blood Stem Cell Transplant for the Treatment of Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Transplant-related mortality at 180 days [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease response (complete response) [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival at 1 year [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: September 2005
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Evaluate transplant-related mortality in patients with multiple myeloma treated with a myeloablative conditioning regimen comprising melphalan and busulfan followed by HLA-matched, allogeneic peripheral blood stem cell transplantation (PBSCT) and graft-vs-host disease prophylaxis with tacrolimus and methotrexate.

Secondary

  • Determine the disease response in patients treated with this regimen.
  • Determine the 1-year progression-free survival and overall survival in patients treated with this regimen.

OUTLINE:

  • Conditioning regimen: Patients receive melphalan IV over 30 minutes on day -6 and busulfan IV over 3 hours on days -5 to -3.
  • Peripheral blood stem cell transplantation (PBSCT): Patients undergo HLA-matched, related donor, allogeneic PBSCT on day 0.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -2 and continuing until day 80 followed by a taper until day 180 in the absence of GVHD or disease progression. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma

    • Stage I disease with disease progression during the second of ≥ 2 lines of prior therapy
    • Stage II or III disease, meeting 1 of the following criteria:

      • Failed to achieve at least a partial response after ≥ 2 courses of prior therapy
      • Progressive disease after ≥ 2 courses of prior therapy
      • Presented with high-risk features at diagnosis, including any of the following:

        • Cytogenetic abnormality
        • Del 13 or 4,14 by fluorescent in situ hybridization (FISH)
        • Elevated lactic dehydrogenase
        • Beta 2 microglobulin > 5.5
        • Circulating peripheral blood plasma cells
    • Any stage disease with disease progression > 6 months after prior autologous stem cell transplantation
  • Availability of an HLA-matched, related donor between 12 and 75 years of age*

    • No bone marrow donors NOTE: *Donors > 75 years of age are eligible at the discretion of the principal investigator

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Creatinine clearance > 60 mL/min
  • Bilirubin ≤ 2.5 mg/dL
  • ALT/AST < 2 times upper limit of normal
  • Cardiac ejection fraction ≥ 49%
  • DLCO ≥ 50% corrected
  • FEV_1 ≥ 60%
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • HIV negative
  • No cirrhosis
  • No chronic inflammatory or fibrotic liver disease

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 6 months since prior autologous transplantation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313625

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: William I. Bensinger, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: William I. Bensinger, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00313625     History of Changes
Other Study ID Numbers: 2018.00, FHCRC-2018.00, CDR0000467231
Study First Received: April 11, 2006
Last Updated: September 20, 2010
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Busulfan
Melphalan
Methotrexate
Tacrolimus
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal

ClinicalTrials.gov processed this record on August 21, 2014